Synthesis, characterization, DFT, docking studies and molecular dynamics of some 3-phenyl-5-furan isoxazole derivatives as anti-inflammatory and anti-ulcer agents

A vast number of nitrogen heterocyclic derivatives comprising oxygen atom is considered as a valuable combination of therapeutic agents in curative chemistry. In particular, isoxazole, a five-member heterocyclic ring, is detected along with some of the marketed drugs such as danazol, flucloxacillin, dicloxacillin, cloxacillin, and valdecoxib which are known as an anti-inflammatory drug. The incorporation of the isoxazole ring can offer enhanced physical-chemical properties to show a wide scope of targets and diverse biological applications. In this view, the title compounds 5(a-h) were synthesized in good yield starting from different substituted benzaldehydes 1(a-h) and 2-acetyl furan (2) to afford chalcone derivatives 3(a-h). Further, compounds 3(a-h) refluxed with hydroxylamine hydrochloride to afford the title compounds 5(a-h). The purified compounds were explained by spectroscopic procedures (FT-IR, H-1 NMR, (CNMR)-C-13, and LC-MS), and lastly, the title compounds 5(a-h) were screened for COX-1, COX-2, LOX furthermore, anti-ulcer action. In-vitro, study reveals that compound (5f) is potent with the IC50 values 9.16 +/- 0.38 mu M (COX-2), 8.15 +/- 0.16 mu M (15-LOX), and 42.41 0.29 pg mL(-1) (anti-ulcer activity against H+/K+ ATPase) which are very close to the standard omeprazole. Besides, in-silico putative binding, possess of compound (5f) was studied by performing molecular docking and molecular dynamic along with ADME/Tox to evaluate its bioavailability and toxicity studies. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study synthesized isoxazole derivatives with therapeutic and anti-inflammatory potential and conducted detailed physical-chemical and biological evaluations. Compound (5f) showed comparable biological activity to the standard drug omeprazole in in-vitro studies. In addition, the bioavailability and toxicity of compound (5f) were evaluated through methods such as molecular docking and molecular dynamics.